The over-all objective of this research is to provide biochemical information that will be channeled to the pharmacological and clinical levels for use in cancer therapy and treatment of bacterial and viral infections. Part I. "Use of the Nucleoside Antibiotics to Elucidate Macromolecular Processes in Mammalian Cells, Tumor Cells, and RNA and DNA Viruses". Previous studies in this laboratory showed that the nucleoside antibiotics play an important role in the elucidation of RNA and DNA synthesis in hyman tumor cells and enzyme systems (ribonucleotide reductase and RNA polymerase). This part of the research represents a logical extension of the application of nucleoside antibiotics in the elucidation of several key cellular reactions. They are: (1) transcription of the provirus genome or murine cells that have been induced to produce leukovirus, (2) the control of DNA synthesis by ribonucleotide reductase, poly(adenosine diphosphate ribose), and DNA polymerase in mammalian, tumor, and bacterial cells, (3) the catalytic characteristics of RNA polymerases, (4) the mechanism of release of viral mRNA from the nucleus, (5) protein synthesis by modifying the 3'- end of tRNA, and (6) RNA replication in the non-ongogenic poliovirus. Part II. "Biosynthesis of Nucleosides and Nucleoside Antibiotics". We will continue studies on the biosynthesis of these compounds because of their importance in DNA and cell reactions. The objectives are: (1) to clarify the role of purines and pyrimidines in the biosynthesis of the C-N and C-C nucleosides and nucleoside antibiotics and (2) to translate the biosynthetic findings to the formation of new nucleoside antibiotics. For example, one of the new nucleoside antibiotics is now being tested at the National Cancer Institute against tumor and cancer cells.